IMPORTANCE This study is needed to clarify inconsistent findings regarding the association between diabetes-related eye complications and psychological well-being. OBJECTIVE To examine the association between severity of diabetic retinopathy (DR) and diabetic macular edema (DME) with symptoms of depression and anxiety in adults with diabetes. DESIGN, SETTING, AND PARTICIPANTS A cross-sectional studywas conducted in a tertiary eye hospital in Melbourne, Australia. The study comprised 519 participants with diabetes. The median duration of diabetes was 13.0 (interquartile range, 14.0) years. The study was conducted from March 1, 2009, to December 24, 2010. EXPOSURES Patients underwent a comprehensive eye examination in which dilated fundus photographs (disc and macula centered) were obtained and graded for the presence and severity of DR and DME. Presenting distance uniocular and binocular visual acuity were assessed using a 3-m logMAR chart. MAIN OUTCOMES AND MEASURES Symptoms of depression and anxietywere measured using the Hospital Anxiety and Depression Scale (HADS), which comprises 7 questions specific to anxiety and 7 specific to depression with scores ranging from 0 to 21; scores higher than 8 signify possible anxiety or depression. The ordinal raw scores of the HADS questionnaire were transformed to estimates of interval measure using Rasch analysis and evaluated as continuous variables. Participants also completed standardized interview-administered questionnaires. Blood samples were assessed for hemoglobin A1c, fasting blood glucose, and serum lipids. Multiple linear regression models were used to determine the associations between the severity of DR and DME with symptoms of anxiety and depression and commonality analysis was used to quantify the unique variance explained. RESULTS Of the 519 participants in the study, 170 individuals (32.8%) were female; mean (SD) age was 64.9 (11.6) years. Raw scores indicated that 80 individuals (15.4%) screened positive for depressive symptoms and 118 persons (22.7%) screened positive for symptoms of anxiety. In multivariate analysis using Rasch scores, severe nonproliferative DR (NPDR)/PDR was independently associated with greater depressive symptoms (regression coefficient [β] = 0.69; 95%CI, 0.03-1.34) after controlling for sociodemographic factors and clinical characteristics, including visual acuity. A history of depression or anxiety accounted for 60.6%(95%CI, 23.9%-83.2%) of the unique variance in depressive symptoms, and severe NPDR or PDR contributed to 19.1%(95%CI, 1.7%-44.4%) of the total explained variance of depressive symptoms. Diabetic macular edema was not associated with depressive symptoms. No association between DR and symptoms of anxiety was identified. CONCLUSIONS AND RELEVANCE Severe NPDR or PDR, but not DME, was independently associated with depressive symptoms. The severity of DR could be an indicator to prompt monitoring of depression in at-risk individuals with diabetes. Further work is required to replicate these findings and determine the clinical significance of the association.